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Principal Investigator/Program Director Williams, Robert W. |
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| Conclusion The complexity of CNS development is staggering. In mice approximately 75 million neurons and 25 million glial cells are generated, moved, killed or connected, and integrated into hundreds of different circuits over a period of 1 month (Williams 2000). The process is coordinated by the expression of a large fraction of the genome—as many as 40,000 genes are involved (Sutcliffe 1988; Adams et al. 1993). These same genes coordinate the development of the human brain, but more than a thousand times as many neurons are generated (Williams and Herrup 1988) and their integration and training take more than a decade. Five thousand genes probably have common roles in cellular metabolism, but another huge complement have selective, transient, and partially redundant roles in the development of different parts of the brain (Usui et al. 1994; Gautvik et al. 1996). Reductionist approaches that focus on isolated genes, molecules, and processes may seem hopelessly inadequate for disentangling the complex genetics of normal brain development, but they are essential at this early stage of analysis and understanding. To begin to understand the design of the brain, whether that of a mouse or a human, we need to extract the key genes that control and modulate cell proliferation, differentiation, and survival. A significant fraction of genes are polymorphic—that is, they exist in multiple forms or alleles—and differences in alleles generate variation in CNS structure that may be subtle or quite extreme. Normal variation is a significant source of the fascinating and sometimes disturbing behavioral differences among humans.
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